PT - JOURNAL ARTICLE
AU - Yamamoto, Masamichi
AU - Beppu, Hideyuki
AU - Takaoka, Katsuyoshi
AU - Meno, Chikara
AU - Li, En
AU - Miyazono, Kohei
AU - Hamada, Hiroshi
TI - Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo
AID - 10.1083/jcb.200808044
DP - 2009 Jan 26
TA - The Journal of Cell Biology
PG - 323--334
VI - 184
IP - 2
4099 - http://jcb.rupress.org/content/184/2/323.short
4100 - http://jcb.rupress.org/content/184/2/323.full
SO - J Cell Biol2009 Jan 26; 184
AB - The anterior–posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.